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The spleen as a bidirectional signal transducer in acute kidney injury. In acute kidney injury models, the lung is damaged through an interleukin-6-dependent inflammatory response. Clinically, development of lung injury requiring mechanical ventilation markedly increases in-hospital acute kidney injury mortality. Andres-Hernando et al. demonstrate that the spleen coordinates interleukin-6-dependent interleukin-10 production, which lessens lung injury during experimental acute kidney injury. This study highlights the beneficial influence of the spleen on the lung, and dovetails with other recent publications, to demonstrate the integral role of the spleen in acute kidney injury.